Search Results (166)

Paroxetine, a selective serotonin reuptake inhibitor commonly used to treat various psychiatric disorders, may adversely affect female reproductive function. Although apigenin has been shown to ameliorate reproductive abnormalities and ovarian dysfunction, its effect on paroxetine-induced reproductive toxicity in females remains unclear. Therefore, this study investigated the potential protective effects of apigenin against paroxetine-induced reproductive alterations in female rats. Female rats with regular estrous cycles were randomly assigned to four groups (n = 9 per group): control, apigenin, paroxetine, and paroxetine + apigenin. The rats received saline, apigenin (20 mg/kg), paroxetine (10 mg/kg), or their combination by oral gavage once daily for about 29 consecutive days. Compared with paroxetine treatment alone, apigenin co-administration restored decreased serum anti-Müllerian hormone (AMH) levels, enhanced PAS reactivity in the zona pellucida, reduced ovarian iNOS immunoreactivity, increased follicle and corpus luteum numbers, and increased ovarian VEGF immunoreactivity. However, apigenin administration alone was associated with reduced testosterone levels and alterations in certain ovarian and uterine histological features in female rats. In conclusion, the findings suggest that apigenin may ameliorate paroxetine-induced reproductive alterations in female rats by modulating AMH levels, follicle and corpus luteum numbers, and ovarian histochemical and molecular parameters. Full article

The Hippo pathway effector Yes-associated protein (YAP), acting through TEA domain (TEAD) transcription factors, regulates transcriptional programs in ovarian tissues; however, its role in interferon tau (IFNT) signaling within bovine luteal cells has not been investigated. This study aimed to determine whether YAP-TEAD interaction is required for IFNT-induced interferon-stimulated gene (ISG) expression in primary bovine luteal cells and to perform an exploratory assessment of selected receptor genes (ITGB1, GRP78, VEGFR2). Primary luteal cells were treated with recombinant ovine IFNT (roIFNT; 1 ng/mL) in the presence or absence of verteporfin (VP; 0.1, 0.5, or 1.0 µM), a pharmacological YAP-TEAD inhibitor, and mRNA expression was quantified by RT-qPCR. VP dose-dependently suppressed YAP target genes (YAP1, CTGF, ANKRD1) and reduced roIFNT-induced expression of MX1, MX2, and OAS1, whereas ISG15 was unaffected. Steroidogenic gene expression (3β-HSD, P450scc, StAR) remained unchanged across treatments, indicating preserved cell viability. Among the exploratory receptor endpoints, VP decreased ITGB1 and increased GRP78 at the highest concentration, while VEGFR2 was unaffected. These findings indicate that YAP-TEAD activity contributes to IFNT-induced ISG responsiveness in bovine luteal cells, with preliminary evidence of effects on integrin-mediated signaling pathways. Full article

Background: Although ovarian cryopreservation is an essential strategy for fertility preservation, ischemia–reperfusion injury and oxidative stress can significantly compromise graft viability after transplantation. Melatonin is a potent antioxidant capable of modulating redox homeostasis and tissue repair; however, its effects on the ovarian microenvironment after cryopreservation are not fully understood. Objective: To investigate whether melatonin supplementation during ovarian cryopreservation enhances GPx1/2-mediated antioxidant defense, preserves follicular integrity, and modulates the angiogenic balance (assessed via VEGF-A expression) after autologous ovarian transplantation in rats. Methods: Twenty-four Wistar rats were ovariectomized and divided into control (standard cryopreservation) and melatonin-treated (0.1 μM melatonin) groups. Ovaries were cryopreserved, thawed, and autotransplanted. After 30 days, the grafts were analyzed for GPx1/2 expression (immunohistochemistry), VEGF-A levels (ELISA), biochemical markers, and follicular integrity (histomorphometry) Results: The melatonin treatment significantly increased GPx1/2 expression in the corpus luteum (p = 0.002), theca interna (p = 0.007), and interstitium (p = 0.012), and reduced the number of degenerated follicles (p = 0.03). Although absolute VEGF-A levels did not differ between groups, melatonin-treated animals showed higher VEGF/FSH ratios (p = 0.0007) and VEGF/LH (p = 0.0494) ratios. Positive correlations were observed between GPx1/2 expression and VEGF-A expression. Conclusions: Melatonin increases antioxidant defenses in cryopreserved ovarian grafts through the upregulation of GPx1/2 and preservation of follicular morphology. Instead of directly increasing VEGF-A levels, melatonin appears to modulate angiogenic signaling, contributing to a more stable microenvironment for ovarian graft survival. Full article

Ovarian function relies on a network of well-coordinated molecular mechanisms that regulate follicular development, oocyte maturation, ovulation, and corpus luteum function. When these processes are disrupted, infertility can result. Extracellular matrix (ECM) remodeling represents a central regulatory component in these processes and is essential for follicle rupture and oocyte release. This mechanism involves metalloproteinases (MMPs), mainly MMP-2 and MMP-9, which degrade the ECM and allow the necessary structural changes. Other ECM-modulating proteases, such as ADAM and ADAMTS families, also contribute to this process. Their activity is tightly regulated by tissue inhibitors of metalloproteinases (TIMPs), ensuring that tissue remodeling occurs in a controlled manner. Disruption of the balance between MMPs and TIMPs increases the risk of infertility-related conditions such as polycystic ovary syndrome (PCOS), endometriosis, luteinizing hormone (LH) deficiency syndrome, and ovarian aging. In addition to the ECM, other factors, including intracellular signaling pathways, oxidative stress (OS), and mitochondrial function, contribute to ovarian physiology and directly affect oocyte quality and viability. This narrative review focuses on the molecular mechanisms governing ovarian function, with particular emphasis on the remodeling of the ECM by MMPs during ovulation, and examines how their disorders contribute to infertility. A deeper understanding of these mechanisms may lead to the identification of new therapeutic targets and the improvement of assisted reproduction outcomes. Full article

Heat stress (HS) affects female reproductive efficiency by disrupting redox homeostasis and activating inflammatory responses in the corpus luteum (CL), a metabolically active tissue essential for pregnancy maintenance. This study reveals the protective effect of resveratrol against HS-induced luteal injury in pregnant mice through the regulation of oxidative stress and cytokine–chemokine-mediated inflammatory and immune responses. The pregnant mice were divided into three groups: control, HS, and resveratrol +HS. Heat stress was applied at 40 ± 0.5 °C for 7 days, with resveratrol (10 mg/kg) given orally 2 h before exposure to HS. The results showed that heat exposure reduced serum total superoxide dismutase activity and increased malondialdehyde level, causing significant disruption of luteal morphology with cellular disorder and vacuolization, which was partially overcome by resveratrol pretreatment. Transcriptomic profiling showed that HS induced a strong immunological and inflammatory response, involving cytokine–cytokine receptor interaction and chemokine signaling. Resveratrol significantly attenuated HS-induced transcriptional changes. The RT-qPCR results showed that HS increased chemokine ligands (Ccl11, Cxcl13, Tslp) and cytokine receptors (Ccr3, Ccr4, Ccr5), which were suppressed by resveratrol. The chemokine-based inflammatory module is one of the most important regulatory properties of the HS response, according to the network analysis. Stable binding of resveratrol with major chemokine receptors was supported by molecular docking and molecular dynamics simulations. Collectively, HS induces oxidative, structural, and inflammatory alterations in luteal tissue, while resveratrol attenuates these changes by being associated with improved antioxidant status and suppression of cytokine–chemokine-mediated responses. Full article

Modern genetic selection for high productivity has created a physiological conflict in ruminants, where the metabolic demands of lactation compete directly with the energy requirements of reproduction. This review provides a mechanistic synthesis of how key nutritional factors modulate the endocrine and cellular pathways governing reproductive success in cattle and sheep. Negative energy balance (NEB), characteristic of the early postpartum period, suppresses the hypothalamic–pituitary–gonadal (HPG) axis by impairing the pulsatile secretion of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH), mediated through reduced kisspeptin signaling, growth hormone (GH) resistance, and decreased circulating insulin, insulin-like growth factor-1 (IGF-1), and leptin. At the macronutrient level, excess rumen-degradable protein elevates blood urea nitrogen and impairs the uterine environment, while omega-3 polyunsaturated fatty acids inhibit prostaglandin F2α synthesis to support corpus luteum maintenance. At the micronutrient level, selenium, copper, and zinc are essential antioxidant cofactors protecting gametes and embryos from oxidative stress, while vitamins A, D, and E regulate gene expression in reproductive tissues. Furthermore, maternal nutrition during critical gestational windows programs the reproductive capacity of offspring through epigenetic modifications, with profound implications for long-term herd fertility. Understanding these nutritional–reproductive interactions is crucial for developing precision feeding strategies that optimize herd fertility, improve animal welfare, and ensure the economic sustainability of livestock management. A thorough understanding of these nutritional–reproductive interactions is essential for developing precision feeding strategies that optimize fertility in high-producing ruminants. Full article

One of the most important aspects of animal production is the reproductive behavior, where a widely used strategy in small ruminants is the “male effect”. However, the response to this effect can vary depending on several factors, including the social rank (SR) of both sexes. The objective of this study was to evaluate how SR influences morphometric and socio-sexual variables in Dorper sheep in Northern Mexico. Through behavioral tests, 33 rams and 59 ewes were divided into two groups taking into account their SR. Rams included high SR (HSR; n = 14) and low SR (LSR; n = 19), while ewes included HSR (n = 23) and LSR (n = 36). Morphometric response variables included age, live weight, body condition, thoracic circumference, wither height, presence of horns, and testicular circumference, whereas reproductive variables included estrus rate, ovulation rate, corpus luteum, left ovary, right ovary, pregnancy rate, and embryos’ number. The results showed no differences (p > 0.05) for the morphometric variables considered, whilst, regarding the reproductive variables, the LSR rams × HSR ewes group showed the highest number of embryos (p < 0.05), and the corpus luteum number was higher in the HSR rams × HSR ewes group (p < 0.05). However, no significant differences were found for the remaining variables (p > 0.05). Improving productive and reproductive performance can contribute to increased income for sheep farmers. Full article

Heat stress (HS) occurs when animals are unable to effectively dissipate excess body heat, leading to increased core temperature and physiological imbalance. In mammals, HS negatively affects female reproduction. Infertility associated with HS is well documented in swine and is increasingly recognized in other mammals, including humans. HS disrupts several systemic processes that are essential for normal reproductive function, including endocrine regulation, nutrient metabolism, immune activity, and intestinal barrier integrity. Reduced feed intake and changes in metabolic hormones such as insulin and prolactin can impair ovarian function. Increased intestinal permeability during HS may allow bacterial endotoxins to enter the bloodstream, triggering inflammation that further compromises reproductive physiology. At the ovarian level, HS alters key cellular pathways involved in cell survival and metabolism, including Janus Kinase/Signal Transducer and Activator of Transcription (JAK–STAT), Phosphoinositide 3-Kinase/Protein Kinase B (PI3K/AKT), oxidative stress responses, autophagy, apoptosis, and heat shock protein expression. These changes disrupt follicular development, hormone production, oocyte quality, and corpus luteum function, resulting in reduced conception rates and increased embryonic loss. This review summarizes current knowledge of systemic and ovarian mechanisms by which HS impairs female reproduction in pigs and identifies areas requiring further investigation to improve fertility under increasing environmental temperatures. Full article

Persistent corpus luteum (PCL) and ovarian quiescence (OQ) are key manifestations of ovarian dysfunction (OD) that lead to reduced reproductive capacity in beef cattle, posing a serious challenge to the industry. Anthocyanins (ACNs) are known for their antioxidant properties. This study aimed to investigate the regulatory effects of ACNs on PCL and OQ and to explore the underlying mechanisms. Forty-eight beef cows diagnosed with both OQ and PCL were selected and continuously fed ACNs for 60 days. The results showed that the regulatory effects of ACNs were dose-dependent. A high dose of ACNs (ACNH) significantly increased the number of large follicles and reduced the occurrence of PCL. ACNH treatment significantly decreased serum progesterone (P4) levels and increased estradiol (E2) levels. Furthermore, ACNH reduced microbial diversity in OD cows but significantly increased the abundance of Patescibacteria, Actinobacteriota, Proteobacteria, and Chloroflexi, while decreasing the abundance of Desulfobactera, indicating that ACNs may affect ovarian function by regulating the gut microbial environment. In an ovarian granulosa cell model of oxidative damage, ACN intervention could reduce oxidative stress levels and mitigate oxidative damage. ACNs downregulated various pro-apoptotic genes, such as P53, Fas, and Bax, while upregulating anti-apoptotic genes Bcl-2 and Bcl-xL, suggesting that ACNs significantly inhibit cell apoptosis. To conclude, these results demonstrate that ACNs improve the ovarian function of beef cows by regulating gut microbiota and reducing oxidative stress-induced apoptosis in ovarian granulosa cells, thereby enhancing the reproductive capacity of beef cattle that show reproductive disorders. These findings provide a theoretical basis for the application of ACNs in the cattle industry and showcase their potential value as natural antioxidants. Full article

The aim of this study was to comparatively evaluate echotextural and hemodynamic changes in the corpus luteum (CL), uterus, and uterine artery, together with serum progesterone (P4) concentrations, using B-mode and Doppler ultrasonography between days 5 and 21 post-insemination in pregnant and non-pregnant cows. Twelve clinically healthy Brown Swiss cows were enrolled and allocated into a cyclic non-inseminated group (n = 6) and an inseminated group (n = 6). Ultrasonographic examinations and progesterone measurements were performed daily during the post-insemination period, and pregnancy was confirmed on day 30. Echotextural parameters (mean gray value and homogeneity) were obtained from the corpus luteum and uterus using B-mode ultrasonography. Doppler ultrasonography was used to assess corpus luteum vascular parameters and uterine artery blood flow, and serum progesterone concentrations were measured at each examination. Corpus luteum mean gray value showed a significant time effect (p < 0.001). For Corpus luteum area and perfusion area, both the time effect and the group × time interaction were significant (p < 0.001), and marked differences between pregnant and non-pregnant cows were observed on days 19, 20, and 21 (p < 0.05). Serum progesterone concentrations also differed significantly between groups on days 20 and 21. In conclusion, changes in corpus luteum area and perfusion area were associated with early pregnancy-related differences and may represent earlier functional ultrasonographic indicators compared with uterine artery Doppler parameters and progesterone concentrations alone. These findings may have practical implications for herd management by potentially enabling differentiation between pregnant and non-pregnant cows approximately 1–2 days earlier than serum progesterone measurements. Full article

In bovine embryo transfer (ET) using in vitro-produced (IVP) embryos, recipient factors and embryo grade are well-established predictors of pregnancy success, but the impact of the laboratory-level developmental competence of IVP embryos remains insufficiently characterized. This retrospective study evaluated factors affecting pregnancy rates following the transfer of IVP beef embryos to dairy recipients. Medical records from 462 ETs were analyzed across three categories: (1) recipient-related factors (parity, body condition, estrus synchronization, corpus luteum characteristics); (2) laboratory factors (cleavage, blastocyst formation, degeneration, embryo grade, developmental stage, cryopreservation); and (3) environmental factors (temperature–humidity index, transport time). Mean comparison and chi-square analyses revealed significant differences in pregnancy rates based on corpus luteum volume, cleavage rates, blastocyst formation rates, degeneration rates, and embryo grade. In binary logistic regression, categorized increases in blastocyst formation rate, degeneration rate, and embryo grade were associated with a 1.45-fold increase, 0.74-fold decrease, and 0.56-fold decrease in pregnancy odds, respectively; no recipient or environmental variables were independent predictors. These findings indicate that developmental competence of IVP embryos is more critical for pregnancy success than recipient or environmental factors, suggesting that optimizing IVP systems to maximize embryo quality is the most effective strategy to improve reproductive efficiency in ET. Full article

The aim of this study was to investigate the effects of dietary supplementation with 0.11% N-carbamylglutamate (NCG) during early pregnancy (0–90 days) on reproductive performance and fetal development, and to elucidate the underlying placental regulatory mechanisms in primiparous Hu sheep. Twenty-two 10-month-old sexually mature primiparous Hu sheep meeting the mating criteria were randomly assigned to two groups. The control group was fed a basal diet, while the NCG group received the basal diet supplemented with 0.11% NCG, with both feeding regimens maintained for 90 days. By measuring uterine and fetal growth indices, maternal plasma biochemical parameters, and amino acid levels, as well as assessing cotyledon indices and observing cotyledon morphology and histological structure, basic data related to placental function and fetal growth in pregnant ewes was collected. Combined with transcriptomic sequencing of maternal placental tissue, the mechanism by which NCG influences placental function and fetal growth and development in pregnant ewes was further investigated. The supplementation of NCG could increase the number of fetuses, total weight of fetuses, the number of corpus luteum and the ratio of fetuses to corpus luteum, but the difference was not significant (p > 0.05). The levels of plasma NO, inducible Nitric Oxide Synthase (iNOS) and several amino acids were significantly increased (p < 0.05). In ewes’ uteri, the average uterine weight, number of uterine glands, total cotyledon weight, and average weight per cotyledon were significantly increased (p < 0.05), whereas uterine mucosal thickness was markedly decreased. The Quantitative Real-time PCR (q-PCR) results for differentially expressed genes were consistent with those of transcriptomic analysis, showing significant changes in the expression levels of certain differentially expressed genes in maternal placental tissues. These changes regulated pathways such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), phosphatidylinositol 3-kinase–protein kinase B (PI3K–AKT) signaling pathways and Mitogen-Activated Protein Kinase (MAPK) pathway, which are involved in angiogenesis, energy supply and metabolism, and somatic growth and development. Dietary supplementation with NCG during early pregnancy can significantly improve the reproductive performance of primiparous Hu sheep, optimize the intrauterine environment and nutrient supply, and thereby facilitate pregnancy maintenance and fetal development. The underlying mechanism may involve promoting endogenous arginine synthesis in ewes, increasing plasma levels of NO, arginine, and certain amino acids, which collectively validate the positive effects of NCG on the reproductive performance and growth of Hu sheep during early pregnancy at the molecular level. Full article

The aim of this study was to evaluate the effect of the linoleic–α-linolenic acid ratio (LA:ALA) on cyclicity, oocyte quality, early pregnancy parameters, milk yield, and composition. Holstein cows were randomized to a 6:1-LA:ALA diet (Low-OMG3: n = 3 pens; 11 primiparous, 14 multiparous) or a 2:1-LA:ALA diet (High-OMG3: n = 3 pens; 10 primiparous, 14 multiparous). Diets were isocaloric and isonitrogenous and fed between 15 and 140 days in milk (DIM). Data were compared using linear mixed models. As expected, omega-3 concentrations in milk and blood increased in the High- compared to Low-OMG3 cows. No effect of diet was observed on cyclicity by 45DIM or oocyte quality at 50DIM. High-OMG3 cows had larger corpus luteum size (11–32 d post-timed artificial insemination [TAI]) and greater blood flow (32–60 d post-TAI) than Low-OMG3 cows. However, there was no effect of diet on progesterone, pregnancy-associated glycoproteins, or conceptus size. High-OMG3 cows produced more milk throughout the study, had greater lactose, and tended to have greater protein yield at 50DIM. In conclusion, decreasing the LA:ALA dietary ratio in lactating dairy cows did not provide evidence of effects on cyclicity, oocyte quality, or other early pregnancy-related parameters, but affected corpus luteum size and blood flow, enhanced milk production, and partially increased protein and lactose yields. Full article

Effective luteal support is crucial for successful pregnancy following embryo transfer in dromedary camels, highlighting the importance of maintaining adequate luteal function. This study compared three luteal support protocols for pregnancy rates after embryo transfer (ET) in dromedary camels. Recipients with a single ovarian follicle (14~16 mm) were assigned into: (1) untreated control, (2) Phenylbutazone (PBZ) at 3.7 mg/kg IV prior to ET, or (3) human chorionic gonadotropin (hCG) 2000 IU plus 3.7 mg/kg IV PBZ prior to ET. Recipients that showed ovarian inactivity were treated with an injection of 1800 IU of equine chorionic gonadotropin (eCG) after progesterone (P₄) priming. Pregnancy was assessed on days 10 (P₄ assay) and 60 (transrectal ultrasonography) post-ET. Pregnancy rates on day 10 were higher in the hCG + PBZ (73.3%) and eCG (68.0%) groups than in the PBZ (44.0%) and control (35.0%) groups (p < 0.05). By day 60, the hCG + PBZ group exhibited the highest pregnancy maintenance rate (81.8%) and the lowest embryonic loss rate (18.2%), compared with eCG (53.0%; 47.0%), PBZ (54.5%; 45.5%), and control (57.1%; 42.9%) groups, respectively (p < 0.05). However, there was no significant difference among the eCG, PBZ, and control groups in embryonic loss rates. In conclusion, hCG synergizes with PBZ to enhance corpus luteum function, uterine receptivity, and pregnancy maintenance more effectively than PBZ or eCG. Full article

Carbofuran, a widely used carbamate pesticide, is an endocrine disruptor with documented reproductive toxicity, yet the mechanisms underlying its ovarian toxicity remain incompletely understood. This study employed integrated network toxicology and untargeted metabolomics to investigate these mechanisms in female C57BL/6J mice that had been chronically exposed to carbofuran (0.5 or 2.0 mg/kg for 45 days, once daily). Methods included histopathological evaluation, serum hormone ELISA, network prediction of toxicity targets, molecular docking, and metabolomics profiling. Results demonstrated that carbofuran exposure induced dose-dependent ovarian damage, including reduced follicular reserve, increased atresia, abnormal corpus luteum, and disrupted hormone levels. Network toxicology identified 38 common targets, with EGFR, GSK3B, APP, and JAK2 as core proteins, indicating potential high affinity. Metabolomics suggests significant alterations in pathways such as phenylalanine, tyrosine, tryptophan biosynthesis and arginine/proline metabolism. Our collective evidence indicates that carbofuran may induce ovarian toxicity through multifaceted mechanisms involving endocrine disruption, oxidative stress, inflammatory activation, and metabolic disturbance. This study provides novel experimental insights into the reproductive toxicity mechanisms of carbofuran, offering a theoretical basis for health risk assessment and intervention strategies. Full article